Thyroid hormone receptors will be studied in animal liver nuclei. Receptor complexes will be purified by affinity chromatography. Binding of receptor complexes to chromatin will be investigated in vitro. The relationship of receptor occupancy and receptor complex to RNA synthesis in vivo and in vitro will be investigated. The enzymatic mechanism of H2O2 production in the thyroid will be studied, especially in regard to the participation of NADPH-Cytochrome c reductase and NADH-Cytochrome B5 reductase. We will study the effect of iodide, TSH, and cyclic nucleotides on these H2O2 generating systems. Physiologic control of hormone production in vivo will be investigated in rats. Thyroid peroxidase will be purified by affinity chromatography and by using insolubilized antibody combining with thyroid peroxidase. The interaction of thyroid colloid droplets and lysosomes will be studied in vitro. Clinical studies will be performed on patients with various thyroid diseases, but specifically on patients with inherited defects in thyroid hormone biosynthesis, transport, or action. Primary attention will be given to analysis of the defect in nuclear receptors in the Gonzales sibship.